Friday, February 17, 2006

Well, the lecture by Jack Szostak was excellent. I had no idea how much progress has been made on pre-cellular evolution. Even though I've read a little bit about the subject, I was still blown away by the some of the research that the Szostak lab has done. I want to summarize everything, but I realize that's just not feasible. So I'll concentrate on some highlights.

Two of life's key features are, without a doubt, self-replication and compartmentalization. Without self-replication, life could never sustain itself and it would lack the main pre-requisite for evolution. So, we're looking for a simple self-replicator, first. Compartmentalization is just as important, because without it the molecules of a would-be living thing would simply diffuse into the environment. The work by Jack Szostak and his colleagues concentrated on the origin of these different systems and how they might have eventually been brought together.

We've now got a handle on how some simple nucleic acid (mostly RNA) self-replicators work. But they're pretty slow and have low-fidelity. Part of the problem is the chemistry of RNA itself. The nucleic acids we know today tend to have a large triphosophate group on them, this forms an "arm" that is negatively charged and would tend to repel rather than attract each other. That sort of slows down the whole self-replication thing. However, Szostak gave some very good reasons for looking elsewhere in "chemical space", as he called it. DNA and RNA, for instance, are not the only nucleic acid polymers out there. They've got a number of close cousins that can do the job also: TNA, GmNA, and GNA to name a few. They all have genetic potential and need to be explored. Diversity, here as in everywhere in evolution, is always that which defeats the small probabilities

There are also other permutations of molecules like DNA and RNA that are 100-fold more efficient at sticking themselves together. They might offer better candidates for self-replicating polymers than the versions modern cells use.

In living cells, compartmentalization is accomplished by membranes formed of fatty acids. Vesicles are self-organizing fatty acid membranes similar in organization to that of living cells. All cells are have such membranes, and they are one of the most cruicial aspects of life -- and they can self-assemble! This has been known for quite some time. But what Szostak and colleagues have been doing is to experiment with vesicles formed of simpler fatty acids, something more likely to have been around 4 billion years ago. Out own cell membranes are made of phospholipids that these cells synthesize. The array of available fatty acids for study shows what looks remarkably like a series of transitional forms between simpler fatty acids such as oleaic acid and our own more complex phospholipids.

Clay has been a major player in the study of the origin of life, since it has been found to have the ability to adsorb RNA to its surface. Szostak and colleagues tried to see what would happen to vesicle self-assembly when a piece of montmorillonite clay was added to the mixture. The results were dramatic: the rate of vesicle self-assembly went from a low linear rate to a steep logarithmic growth! What's more is that when clay with RNA adsorbed to it was used, many of the resulting vesicles could be seen to have the RNA inside of them!

One of the most interesting experiments was testing how different sugars would flow into/out of these fatty acid vesicles. Of the five or so sugars that was tested, ribose was -- by some considerable measure -- the most efficiently uptaken. Why is this important? Well, ribose is the R of RNA (ribonucleic acid). Ribose is the sugar out of which nucleic acids are made. This may explain why we use ribose in our own genetic information, since any proto-cell using ribose for its genetic material would've been at a significant competitive advantage.

What's really interesting about all this is that so many of these reactions are spontaneous. That is, they're energetically favrouable, at least under the conditions that were given. So, what's going on is that this isn't just people synthesizing the components of life in the lab, but the observation of the actual processes involved. I can't help but feeling ridiculously optimistic about have spontaneously generating protocells in the tube before I'm a middle-aged man.

I think these highlights just scratch the surface. I want to cover some more about the lecture, so I'll defer that to another post on Saturday or Monday.

4 comments:

Anonymous
said...

Martin wrote "What's really interesting about all this is that so many of these reactions are spontaneous. That is, they're energetically favourable, at least under the conditions that were given. So, what's going on is that this isn't just people synthesizing the components of life in the lab, but the observation of the actual processes involved."

That is _very_ interesting! I'm now (finally!) reading Davies "The Fifth Miracle", and I've just got to the part where he complains that some of the reactions he thinks necessary are thermodynamically unfavorable. I look forward to comparing his (1999) views with Szostak's.

Yeah, but I think catalysts are the mainstay in a lot of these processes. Still, Szostak talked about the mechanics of vesicle formation which is not yet very well understood. However, spontaenous vesicle formation is highly complex (hmm!) and intermediate structures are thought to catalyze the formation of later ones.

He also talked about spontaneous primer extension. Now, my chemistry is a little rusty, but he talked about how nucleotides (nucleosides?) with a much stronger nucleophile will drive this process 100-fold faster.

Check out the review in this weeks Nature of the introductory book Genesis: The Scientific Quest for Life's Origins by Robert M. Hazen. I think I'll try and get hold of it, despite the unfortunate title.

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About Me

Research Fellow at NCB Naturalis in Leiden, the Netherlands. My research interests include the fossil record and early evolutionary history of jawed vertebrates. The opinions expressed on this blog are my own and do not necessarily reflect those of NCB Naturalis.